FIGURE 2.
PRI‐724 reduces bile acid (BA) synthesis in Mdr2‐KO mice. Male Mdr2‐KO mice (8–10 weeks old, n = 12) and FVB background control mice (n = 6) were treated or not with PRI‐724 (20 mg/kg, 3 times a week) for 10 weeks. (A) Immunohistochemical staining using anti‐S100A4, F4/80, and Ki67 antibodies (scale bars, 250 μm). (B) Quantification of S100A4‐positive and F4/80‐positive cells and GS‐positive areas in the livers. (C) Clustergrams of PCR array analyses of WNT/β‐catenin‐related genes (left panel, WNT/β‐catenin signals; right panel, WNT/β‐catenin targets). (D) Early growth response‐1 (Egr‐1) mRNA expression in the livers as determined by real‐time quantitative PCR (n = 10 per group). (E) Immunohistochemical staining using anti‐Egr‐1 antibodies (scale bar, 100 μm). (F) Quantification of Egr‐1‐positive cells and glutamine synthetase (GS)–positive areas in the livers. (G) Hepatic and serum total BA (TBA), cholic acid (CA), and chenodeoxycholic acid (CDCA) levels (n = 10 per group). The results shown are representative of at least three independent experiments. Data represent the mean ± SD; *p < 0.05, **p < 0.01, ***p < 0.005, and ****p < 0.0001, by Student's t test.